Phase II study of lapatinib in combination with trastuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer: Clinical outcomes and predictive value of early [¹⁸F]fluorodeoxyglucose positron emission tomography imaging (TBCRC 003)

Purpose: Lapatinib plus trastuzumab improves outcomes relative to lapatinib alone in heavily pretreated, human epidermal growth factor receptor 2-positive metastatic breast cancer (MBC). We tested the combination in the earlier-line setting and explored the predictive value of [¹⁸F]fluorodeoxyglucose positron emission tomography ([¹⁸F]FDG-PET) for clinical outcomes. Patients and Methods: Two cohorts were enrolled (cohort 1: no prior trastuzumab for MBC and ≥ 1 year from adjuvant trastuzumab, if given; cohort 2: one to two lines of chemotherapy including trastuzumab for MBC and/or recurrence < 1 year from adjuvant trastuzumab). The primary end point was objective response rate by RECIST v1.0; secondary end points included clinical benefit rate (complete response plus partial response plus stable disease ≥ 24 weeks) and progression-free survival. [¹⁸F]FDG-PET scans were acquired at baseline, week 1, and week 8. Associations between metabolic response and clinical outcomes were explored. Results: Eighty-seven patients were registered (85 were evaluable for efficacy). The confirmed objective response rate was 50.0% (95% CI, 33.8% to 66.2%) in cohort 1 and 22.2% (95% CI, 11.3% to 37.3%) in cohort 2. Clinical benefit rate was 57.5% (95% CI, 40.9% to 73.0%) in cohort 1 and 40.0% (95% CI, 25.7% to 55.7%) in cohort 2. Median progression-free survival was 7.4 and 5.3 months, respectively. Lack of week-1 [¹⁸F]FDG-PET/computed tomography ([¹⁸F]FDG-PET/CT) response was associated with failure to achieve an objective response by RECIST (negative predictive value, 91% [95% CI, 74% to 100%] for cohort 1 and 91% [95% CI, 79% to 100%] for cohort 2). Conclusion: Early use of lapatinib and trastuzumab is active in human epidermal growth factor receptor 2-positive MBC. Week-1 [¹⁸F]FDG-PET/CT may allow selection of patients who can be treated with targeted regimens and spared the toxicity of chemotherapy.